Enter the text here that is the new abstract information for your application. This section must be no vii longer than 30 lines of text. Human brucellosis, caused by Bruce/Ia spp., is one of the most widespread zoonotic diseases globally, with an estimated 500,000 new cases each year. An important aspect of B. abortus infection is its ability to persist within phagocytic cells of the reticuloendothelial system. We have shown that the virB locus, encoding a Type IV secretion system (T4SS), is essential for survival in phagocytes and virulence in mice. However, the mechanisms by which the T4SS allows B. abortus to establish its niche in the host are unknown. The objective of this application is to characterize the role of molecules secreted by the B. abortus T4SS in interaction with host cells. The central hypothesis of this application is that the T4SS functions in establishing a replicative niche in the host by can D-0 O-0 0 fl) E (fl targeting the Bruce//a-containing vacuole to the endoplasmic reticulum (ER). The rationale for the proposed research is that characterization of virulence mechanisms v,' excellent research environment that is highly conducive to its successful completion. The central hypothesis will be tested and the objectives of this application accomplished by pursuing the following specific aim: (i) Determine the contribution of T4SS-translocated effector proteins to persistent infection of the reticuloendothelial system significantly influencing concepts and methods driving the field.